Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to determine whether normal fibrinogen contributes to the development of myocardial reperfusion injury by acting as a substrate in vivo for neutrophil adhesion. This was tested in a dog model of acute myocardial infarction that used pentobarbital anesthetized dogs subjected to 90 min regional myocardial ischemia and 5 h reperfusion. Dogs were treated with 1 unit/kg Ancrod (venom from the Malayan pit viper, Agkistrodon rhodostoma) or vehicle i.v. 60 min after left circumflex coronary artery occlusion. Therapeutic defibrination was verified in Ancrod-treated dogs by measurements of clottable fibrinogen, alpha-2 antiplasmin and plasminogen, by the activated partial thromboplastin time and by immunoelectrophoresis. Fibrinogen was depleted to below detectable limits of the assay (less than 0.05 mg/ml) after treatment with Ancrod. The defibrination effect was accomplished by the expected activation of the fibrinolytic system: alpha-2 antiplasmin was decreased by 10% and plasminogen activity was decreased by 30% with Ancrod treatment. There were no measureable differences between the two treatment groups in heart rate, mean arterial blood pressure, rate pressure product or circumflex coronary blood flow throughout the 90 min of regional ischemia or during the 5 h of reperfusion. The relative severity of ischemia between the two treatment groups was similar when assessed with radiolabeled microsphere measurement of myocardial blood flow. The accumulation of neutrophils (measured by myeloperoxidase activity) within the myocardium after reperfusion was not reduced by prior depletion of fibrinogen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Therapeutic defibrination with ancrod does not protect canine myocardium from reperfusion injury. 170 37

Predictable vascular responses to burn injury can occur where blood vessels are occluded in and just beneath the site of trauma. The loss of vascular patency is linked to the development of ischemia in the surrounding skin. Several mechanisms may be responsible for this occlusion, and their identification will provide a logical means for prevention or reversal of the occlusion. The role of fibrin deposition was investigated here using a rat burn model. If an intravascular fibrin clot is a primary cause of early occlusion, the depletion of circulating fibrinogen should prevent its deposition. Ancrod, a pit viper venom trypsin-like proteinase, when given systemically, converts fibrinogen into a soluble product which does not clot. In studies here, the host is depleted of fibrinogen by intravenous injections of ancrod for 3 days before standard burn trauma. Burn injury in defibrinogenized rats resulted in greatly reduced local vascular occlusion. These results support the idea that vascular occlusion caused by burn injury is dependent on the deposition of fibrin. It is conjectured that the vascular occlusion of burn injury can be reversed by preventing or breaking down intravascular fibrin clots.
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PMID:Ancrod prevents vascular occlusion in thermally injured rats. 357 90

Patients with heparin-induced thrombocytopenia (HIT) require an alternative antithrombotic treatment to heparin during arterial reconstruction. Ancrod and Iloprost have been employed but are not readily available and carry the risks of systemic side effects (depletion of fibrinogen, hypotension). A patient with HIT in whom intraoperative intraarterial urokinase (UK) was successfully utilized to enable safe arterial reconstruction is described. An 80 year old white female with diffuse arteriosclerotic cardiovascular disease and multiple vascular reconstructions had thrombotic complications following use for heparin during two of her prior operations associated with documented thrombocytopenia and anti-platelet antibodies. She presented with limb-threatening ischemia which was evaluated with angiography revealing severe stenosis of the proximal left superficial femoral artery, occlusion of both anterior tibial and peroneal arteries and several digital vessels, with intact posterior tibial runoff. A common femoral to mid-superficial femoral artery bypass was performed, utilizing contralateral reversed greater saphenous vein, while being treated with aspirin and a continuous intravenous infusion of low molecular weight dextran. During the procedure the clamped arteries were locally perfused with a high volume of dilute UK solution to prevent blood stasis, and enable local delivery of a thrombolytic agent. Although clot formation was observed in the operative field, none occurred within the clamped arteries. A total of 191,200 units of UK were employed with no bleeding complications. Following surgery the patient had a palpable pedal pulse and markedly improved perfusion of her toes. She was discharged on aspirin and coumadin on postoperative day five. It is concluded that for patients with HIT, systemic aspirin and dextran combined with local intraarterial UK are a simple and effective substitute for systemic anticoagulation with heparin during arterial reconstruction.
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PMID:Intraoperative urokinase as an alternative to heparin for patients with suspected heparin-induced thrombocytopenia requiring arterial reconstruction: report of a case and review of the literature. 894 86

The development of promising acute stroke treatments is the fruit of the growing appreciation for the complex biochemical processes within neuronal tissue that commence immediately after the onset of ischemia. These biochemical cascades can be modified either by direct pharmacologic mitigation or by rapid restoration of perfusion and oxygenation. With both interventions, the ischemic tissue can remain viable and regain neurologic function rather than progress to infarction. Today the two major pharmacologic approaches to stroke therapy are neuroprotectants and thrombolytics. Neuroprotectants enable neuronal tissues to tolerate periods of minimal perfusion better, whereas thrombolytics facilitate reperfusion by disrupting the fresh thrombus. Important classes of neuroprotectants include calcium channel antagonists, N-methyl-D-aspartate (NMDA) receptor antagonists, benzothiazoles, and free radical scavengers. Pro-urokinase is a potentially important investigational thrombolytic. Ancrod, a defibrinogenating agent, is also currently being evaluated in acute stroke.
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PMID:The stroke pharmacopeia: promising experimental therapies. 961 94